10
Food, drug, insect sting allergy, and anaphylaxis Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children Supinda Bunyavanich, MD, MPH, a,b,c Sheryl L. Rifas-Shiman, MPH, d,e Thomas A. Platts-Mills, MD, f Lisa Workman, BA, f Joanne E. Sordillo, ScD, e,g Carlos A. Camargo, Jr, MD, DrPH, e,g,h Matthew W. Gillman, MD, SM, d,e Diane R. Gold, MD, MPH, e,g,i and Augusto A. Litonjua, MD, MPH e,g,i New York, NY, Boston, Mass, and Charlottesville, Va Background: Maternal diet during pregnancy may affect childhood allergy and asthma. Objective: We sought to examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma. Methods: We studied 1277 mother-child pairs from a US prebirth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age, 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum-specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood. Results: Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least 1 food allergen (28.0%). Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs, 3.6 to 8.1). Conclusion: Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma. (J Allergy Clin Immunol 2014;133:1373-82.) Key words: Maternal diet, pregnancy, food allergy, sensitization, asthma, allergic rhinitis, peanut, milk, wheat, childhood Discuss this article on the JACI Journal Club blog: www.jaci- online.blogspot.com. Allergy and asthma are growing as clinical and public health problems in the United States. 1,2 Recent data suggest that approximately 5% of the US population has food allergy 1 and 8.4% has asthma. 2 Intrauterine exposures may play a role in the development of childhood allergy and asthma because the immune system takes form during the fetal period. 3,4 Research on the effects of early-life exposures—such as maternal diet during pregnancy—on childhood allergy and asthma development could inform primary prevention. The American Academy of Pediatrics previously advised that ‘‘no maternal dietary restrictions during pregnancy are necessary with the possible exception of excluding peanuts.’’ 5 Subsequent systematic reviews of the literature concluded that the current evidence is inadequate to support any dietary re- strictions during pregnancy. 6-9 Most of the studies on this topic have been conducted in populations selected for allergic propen- sity, 10-14 rendering inference to the general population chal- lenging. Furthermore, previous studies of the potential effect of maternal diet during pregnancy have examined only the last month or trimester of pregnancy 10-18 and analyzed outcomes only in the first year(s) of life. 10-13,16-18 Because many cells thought to be involved in the pathogenesis of allergy and asthma are formed during early pregnancy, 19,20 an examination of expo- sures during the first and second trimesters could be worthwhile. Furthermore, studying the potential effects of such exposures beyond early childhood could help with clinical counseling. In this article, we characterize the association between maternal diet during early pregnancy and risk of childhood allergy and asthma in mid-childhood in a US prebirth cohort unselected for any disease. In particular, we focused on maternal intake of foods containing common childhood food allergens From a the Division of Pediatric Allergy and Immunology, Department of Pediatrics, b the Department of Genetics and Genomic Sciences, and c the Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York; d the Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston; e Harvard Medical School, Boston; f the Asthma and Allergic Diseases Center, Univer- sity of Virginia Health System, Charlottesville; g the Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston; h the Department of Emergency Medicine, Massachusetts General Hospital, Boston; and i the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston. This study was supported by the National Institutes of Health (grant nos. AI093538, HL61907, HL64925, HD34568, AI35786, HL68041, AI102960, and HL007427). Disclosure of potential conflict of interest: S. Bunyavanich, S. L. Rifas-Shiman, L. Workman, J. E. Sordillo, C. A. Camargo, and M. W. Gillman have received research support from the National Institutes of Health (NIH). T. A. Platts-Mills has received research support from the NIH and Phadia Thermo Fisher. D. R. Gold has received research and travel support from the NIH. A. A. Litonjua has received grants from the NIH and receives royalties from Springer Humana Press and UpToDate, Inc. Received for publication September 30, 2013; revised November 18, 2013; accepted for publication November 19, 2013. Available online February 9, 2014. Corresponding author: Supinda Bunyavanich, MD, MPH, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place #1198, New York, NY 10029. E-mail: [email protected]. 0091-6749/$36.00 Ó 2014 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaci.2013.11.040 1373

Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

  • Upload
    others

  • View
    2

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

Food, drug, insect sting allergy, and anaphylaxis

Peanut, milk, and wheat intake during pregnancy isassociated with reduced allergy and asthma in children

Supinda Bunyavanich, MD, MPH,a,b,c Sheryl L. Rifas-Shiman, MPH,d,e Thomas A. Platts-Mills, MD,f Lisa Workman, BA,f

Joanne E. Sordillo, ScD,e,g Carlos A. Camargo, Jr, MD, DrPH,e,g,h Matthew W. Gillman, MD, SM,d,e

Diane R. Gold, MD, MPH,e,g,i and Augusto A. Litonjua, MD, MPHe,g,i New York, NY, Boston, Mass, and Charlottesville, Va

Background: Maternal diet during pregnancy may affectchildhood allergy and asthma.Objective: We sought to examine the associations betweenmaternal intake of common childhood food allergens duringearly pregnancy and childhood allergy and asthma.Methods: We studied 1277 mother-child pairs from a USprebirth cohort unselected for any disease. Using food frequencyquestionnaires administered during the first and secondtrimesters, we assessed maternal intake of common childhoodfood allergens during pregnancy. In mid-childhood (mean age,7.9 years), we assessed food allergy, asthma, allergic rhinitis,and atopic dermatitis by questionnaire and serum-specific IgElevels. We examined the associations between maternaldiet during pregnancy and childhood allergy and asthma.We also examined the cross-sectional associations betweenspecific food allergies, asthma, and atopic conditionsin mid-childhood.Results: Food allergy was common (5.6%) in mid-childhood, aswas sensitization to at least 1 food allergen (28.0%). Highermaternal peanut intake (each additional z score) during the firsttrimester was associated with 47% reduced odds of peanutallergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94).Higher milk intake during the first trimester was associatedwith reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic

From athe Division of Pediatric Allergy and Immunology, Department of Pediatrics, bthe

Department of Genetics and Genomic Sciences, and cthe Mindich Child Health and

Development Institute, Icahn School of Medicine at Mount Sinai, New York; dthe

Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston;eHarvard Medical School, Boston; fthe Asthma and Allergic Diseases Center, Univer-

sity of Virginia Health System, Charlottesville; gthe Channing Division of Network

Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston; hthe

Department of Emergency Medicine, Massachusetts General Hospital, Boston; andithe Division of Pulmonary and Critical Care Medicine, Department of Medicine,

Brigham and Women’s Hospital, Boston.

This study was supported by the National Institutes of Health (grant nos. AI093538,

HL61907, HL64925, HD34568, AI35786, HL68041, AI102960, and HL007427).

Disclosure of potential conflict of interest: S. Bunyavanich, S. L. Rifas-Shiman, L.

Workman, J. E. Sordillo, C. A. Camargo, and M. W. Gillman have received research

support from the National Institutes of Health (NIH). T. A. Platts-Mills has received

research support from the NIH and Phadia Thermo Fisher. D. R. Gold has received

research and travel support from the NIH. A. A. Litonjua has received grants from

the NIH and receives royalties from Springer Humana Press and UpToDate, Inc.

Received for publication September 30, 2013; revised November 18, 2013; accepted for

publication November 19, 2013.

Available online February 9, 2014.

Corresponding author: Supinda Bunyavanich, MD, MPH, Icahn School of Medicine at

Mount Sinai, One Gustave L Levy Place #1198, New York, NY 10029. E-mail:

[email protected].

0091-6749/$36.00

� 2014 American Academy of Allergy, Asthma & Immunology

http://dx.doi.org/10.1016/j.jaci.2013.11.040

rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheatintake during the second trimester was associated with reducedatopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat,and soy allergy were each cross-sectionally associated withincreased childhood asthma, atopic dermatitis, and allergicrhinitis (ORs, 3.6 to 8.1).Conclusion: Higher maternal intake of peanut, milk, and wheatduring early pregnancy was associated with reduced odds ofmid-childhood allergy and asthma. (J Allergy Clin Immunol2014;133:1373-82.)

Key words: Maternal diet, pregnancy, food allergy, sensitization,asthma, allergic rhinitis, peanut, milk, wheat, childhood

Discuss this article on the JACI Journal Club blog: www.jaci-online.blogspot.com.

Allergy and asthma are growing as clinical and public healthproblems in the United States.1,2 Recent data suggest thatapproximately 5% of the US population has food allergy1 and8.4% has asthma.2 Intrauterine exposures may play a role inthe development of childhood allergy and asthma because theimmune system takes form during the fetal period.3,4 Researchon the effects of early-life exposures—such as maternaldiet during pregnancy—on childhood allergy and asthmadevelopment could inform primary prevention.

The American Academy of Pediatrics previously advisedthat ‘‘no maternal dietary restrictions during pregnancy arenecessary with the possible exception of excluding peanuts.’’5

Subsequent systematic reviews of the literature concludedthat the current evidence is inadequate to support any dietary re-strictions during pregnancy.6-9 Most of the studies on this topichave been conducted in populations selected for allergic propen-sity,10-14 rendering inference to the general population chal-lenging. Furthermore, previous studies of the potential effect ofmaternal diet during pregnancy have examined only the lastmonth or trimester of pregnancy10-18 and analyzed outcomesonly in the first year(s) of life.10-13,16-18 Because many cellsthought to be involved in the pathogenesis of allergy and asthmaare formed during early pregnancy,19,20 an examination of expo-sures during the first and second trimesters could be worthwhile.Furthermore, studying the potential effects of such exposuresbeyond early childhood could help with clinical counseling.

In this article, we characterize the association betweenmaternal diet during early pregnancy and risk of childhoodallergy and asthma in mid-childhood in a US prebirth cohortunselected for any disease. In particular, we focused on maternalintake of foods containing common childhood food allergens

1373

Page 2: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

J ALLERGY CLIN IMMUNOL

MAY 2014

1374 BUNYAVANICH ET AL

Abbreviations used

FFQ: F

ood frequency questionnaire

NHANES: N

ational Health and Nutrition Examination Survey

OR: O

dds ratio

sIgE: S

pecific IgE

(peanut, milk, wheat, egg, and soy) during early pregnancy.Because data on food allergen sensitization in US populationsunselected for any disease are limited to a few childhood foodallergens,21,22 we also present our cross-sectional findings onfood allergen sensitization and associations between specificfood allergies, asthma, and atopic conditions.

METHODS

Study design and subjectsParticipants of the Project Viva prebirth cohort were recruited from a large

multispeciality practice in Massachusetts. The goal of this longitudinal

epidemiologic cohort was to study dietary factors that could affect health in

early life. Health was broadly defined to encompass diverse areas. Participants

were not selected for any disease. Study details have been previously

described.23

Enrollment occurred between 1999 and 2002 for women with singleton

pregnancy. In-person interviews and questionnaires were administered after

the initial prenatal visit, at an average of 10 weeks of gestation, and at 26 to 28

weeks of gestation. Interviews and questionnaires on child health were

administered at 6 months, 1 year, and annually thereafter. We collected

outcome data for this study at the mid-childhood in-person visit (mean age,

7.9 years). Study protocols were approved by the institutional review boards of

participating institutions. Of the 2128 children delivered in Project Viva, we

included 1277 mother-child pairs who presented for an in-person interview at

mid-childhood.

Maternal dietary assessment during pregnancyMaternal dietary assessments at the first and second trimester visits were

based on a validated 166-item semiquantitative food frequency questionnaire

(FFQ) modified for pregnancy24 and have been previously described (see this

article’s Online Repository for additional details at www.jacionline.

org).23,25,26 The total servings per day of each major food allergen (peanut,

milk, wheat, egg, and soy) were calculated by summing the servings per

day of the foods on the FFQ containing these respective food allergens. We

derived z scores for the servings per day of each major food allergen that

were standardized to a mean of 0 and an SD of 1. We chose to use z scores

to (1) allow readers to more easily compare results across different food

allergens, which had varying distributions for servings per day, and (2) aid

with interpretation of food allergens with mean servings of less than 1 per day.

Childhood outcomesQuestions for asthma, allergic rhinitis, and atopic dermatitis were from the

International Study of Asthma and Childhood.27 Current asthma was defined

as positive if a mother reported at the mid-childhood visit that her child ever

had doctor-diagnosed asthma plus either use of asthma medication or

wheezing in the past 12 months. Current allergic rhinitis was defined as

positive if a mother reported that her child had a runny nose or sneezing apart

from colds in the past 12 months. Current atopic dermatitis was defined as

positive if a mother reported at the mid-childhood visit that her child ever

had doctor-diagnosed eczema plus an itchy rash in the folds of the elbows,

behind the knees, in front of the ankles, under the buttocks, or around the

neck, ears, or eyes in the past 12 months that did not go completely away

for at least 6 months. Ever asthma, ever allergic rhinitis, and ever atopic

dermatitis were defined as positive if a mother reported a doctor’s diagnosis

of each respective condition in the child in any questionnaire since birth.

Maternal and paternal asthma, allergic rhinitis, and atopic dermatitis were

each considered positive if a mother reported at week 10 of gestation that

she or the child’s biological father had a history of the respective condition.

Maternal asthma and allergy (henceforth ‘‘maternal atopy’’) was considered

positive if maternal asthma, allergic rhinitis, or atopic dermatitis was positive;

the analogouswas used to define paternal atopy. Parental atopywas considered

positive if maternal or paternal atopy was positive.

Of the 1277 children who presented for an in-person interview at

mid-childhood, 699 (55.0%) agreed to have blood drawn and 616 (87.7% of

those with blood samples) children had sufficient sample to measure allergen-

specific IgE (sIgE) levels by Phadia ImmunoCAP. Sensitization to a food

allergen was considered positive if the respective allergen sIgE level was 0.35

kU/L or more. Prescription of an epinephrine autoinjector was assessed with

the question, ‘‘Has a health care professional, such as a doctor, physician

assistant, or nurse practitioner, ever prescribed an EpiPen for your child?’’

A childwas considered to have food allergy to peanut,milk, wheat, egg, and/or

soy if he or she had an sIgE level of 0.35 kU/L or more to the particular food

and EpiPen prescribed. For further details, please see the Online Repository at

www.jacionline.org. In addition, we assessed peanut allergy specifically given

the rising prevalence of peanut allergy at the inception of this cohort study28; a

child was considered to have had a peanut allergic reaction if his or her mother

answered yes to the question, ‘‘Has your child ever had an allergic reaction to

peanuts?’’ and yes to at least 1 of the following categories of allergic reaction

symptoms with peanut ingestion: ‘‘Skin related (eg, hives and swelling),’’

‘‘Respiratory (eg, shortness of breath, wheezing, and cough),’’ ‘‘Cardiovascu-

lar (eg, low blood pressure, dizziness, or fainting),’’ ‘‘Gastrointestinal

(eg, vomiting and diarrhea),’’ or ‘‘Anaphylaxis (severe, multisystem allergic

reaction).’’ Assessment of food allergy based on report of convincing

IgE-mediated reaction symptoms such as those covered by our questions

has been shown to be effective, with only a 7% false-positive rate.29

Statistical analysesTo assess the associations between maternal diet during the first and second

trimesters of pregnancy and allergy and asthma outcomes, we created

multivariable logistic regression models using food allergen z score as the

unit for maternal dietary intake. Models with food sensitization or food allergy

as the outcome were constrained to the 616 subjects with sIgE levels. Because

the associations between specific childhood food allergies, asthma, and atopic

conditions have not beenwell characterized,we additionally usedmultivariable

logistic regression to assess the cross-sectional associations between food al-

lergy and current asthma, current allergic rhinitis, and current atopic dermatitis.

Given the known associations between food allergy and sex,30 age,30 family

history of allergy,30,31 maternal education,32 and breast-feeding,32 we adjusted

all models for these variables (model 1). We created secondary models

additionally adjusted for race/ethnicity (model 2). Althoughwe anticipated po-

wer limitations, we also created secondary models stratified by parental atopy.

We performed all analyses using SAS 9.3 (SAS Institute, Cary, NC).

RESULTS

Study populationThe baseline characteristics of the participants are shown in

Table I. Compared with the 851 participants excluded, the 1277participants included showed higher proportions of maternalwhite race (69% vs 62%), college or graduate education (69%vs 58%), annual household income exceeding $70,000 (63% vs58%), and parental atopy (59% vs 56%). Compared with the gen-eral US population,33 there was a higher proportion of blacks anda lower proportion of Hispanics among participants. Most of themothers were college educated, and most households were notlow income. Rates of parental asthma, allergic rhinitis, and atopicdermatitis were consistent with those for the general US popula-tion.34-36 Consistent with previous observations demonstratingunderdiagnosis of allergic rhinitis by physicians,37 the prevalenceof current allergic rhinitis (definition based on current symptoms)

Page 3: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

TABLE I. Parental and child characteristics among participants

from the Project Viva prebirth cohort

Characteristic

Participants with

mid-childhood

data (N 5 1277)

Participants with

mid-childhood data

and sIgE levels

measured (N 5 616)

Parental characteristics

Maternal education >_

college graduate

881 (69.3) 407 (66.5)

Household income >_ $70,000 733 (63.0) 359 (64.2)

Maternal atopy 510 (40.1) 241 (39.4)

Maternal asthma 161 (12.7) 84 (13.7)

Maternal allergic rhinitis 376 (29.6) 167 (27.3)

Maternal atopic dermatitis 167 (13.1) 72 (11.8)

Paternal atopy 433 (34.6) 200 (33.2)

Paternal asthma 146 (11.8) 71 (12.0)

Paternal allergic rhinitis 324 (26.7) 154 (26.5)

Paternal atopic dermatitis 76 (6.1) 29 (4.9)

Maternal intake during pregnancy (servings/d)

First trimester

Peanut 0.34 6 0.44 0.34 6 0.48

Milk 1.16 6 1.04 1.17 6 1.07

Wheat 2.65 6 1.48 2.64 6 1.44

Egg 0.32 6 0.30 0.32 6 0.28

Soy 0.08 6 0.27 0.08 6 0.29

Second trimester

Peanut 0.36 6 0.43 0.35 6 0.42

Milk 1.50 6 1.82 1.52 6 1.85

Wheat 2.69 6 1.44 2.66 6 1.41

Egg 0.33 6 0.30 0.33 6 0.29

Soy 0.08 6 0.28 0.09 6 0.34

Child characteristics

Sex: female 632 (49.5) 302 (49.0)

Age (y) 7.93 6 0.82 7.82 6 0.71

Race

White 831 (65.2) 383 (62.4)

Black 199 (15.6) 121 (19.7)

Hispanic 53 (4.2) 30 (4.9)

Asian 43 (3.4) 13 (2.1)

>1 race or other 149 (11.7) 67 (10.9)

Breast-fed >_6 mo 662 (55.6) 319 (55.5)

Child food sensitization

and food allergy

Food allergen sensitization 168 (28.0)

Peanut 85 (13.8)

Milk 96 (15.9)

Wheat 77 (12.9)

Egg 50 (8.3)

Soy 47 (7.9)

Food allergy 32 (5.6)

Peanut 29 (4.9)

Milk 13 (2.3)

Wheat 16 (2.8)

Egg 7 (1.2)

Soy 18 (3.2)

EpiPen prescribed 45 (7.6)

Peanut allergic reaction 27 (4.6)

Child asthma and atopy

Asthma-ever 277 (22.3) 137 (22.5)

Asthma-current 219 (19.6) 105 (19.2)

Allergic rhinitis-ever 291 (23.5) 145 (23.8)

Allergic rhinitis-current 389 (33.6) 199 (34.1)

Atopic dermatitis-ever 306 (24.7) 149 (24.4)

Atopic dermatitis-current 75 (7.4) 42 (8.3)

Values are n (%) or mean 6 SD.

J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 5

BUNYAVANICH ET AL 1375

was higher than the prevalence of ever allergic rhinitis (defined onthe basis of physician’s diagnosis).

Association between maternal intake during

pregnancy and current outcomes at mid-childhoodDistributions of maternal intake of each food allergen during

pregnancy are given in Table I. For additional FFQ results, seeTables E1 and E2 in this article’s Online Repository at www.jacionline.org. Each additional z score of maternal peanut intakeduring the first trimester was associated with a 47% reduced oddsof peanut allergic reaction in childhood (odds ratio [OR], 0.53;95%CI, 0.30-0.94) (Fig 1; see Table E3 in this article’s Online Re-pository at www.jacionline.org). We focus on results of model 1because child’s race/ethnicity was highly collinear with maternaleducation in our sample (x2 5 187.9; P < .0001), and models con-taining collinear terms (ie, model 2) can yield inaccurate results forindividual predictors.38 We did not observe associations betweenfirst-trimester peanut intake and current asthma or other atopic out-comes, nor between second-trimester peanut intake and current out-comes (Fig 2; see Table E4 in this article’s Online Repository atwww.jacionline.org). Each additional z score of maternal milkintake during the first trimester was associated with reduced oddsof current asthma (OR, 0.83; 95% CI, 0.69-0.99) and currentallergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97) (Fig 1; Table E3).We did not detect these associations with second-trimester milkintake (Fig 2; Table E4). Maternal wheat intake during the secondtrimesterwas associatedwith reduced odds of current atopic derma-titis (OR, 0.64; 95%CI, 0.46-0.90) (Fig 2; Table E4). Results of themodels stratifiedbyparental atopy are shown inTables E5andE6 inthis article’s Online Repository at www.jacionline.org. Of note,maternal intakes of peanut, milk, wheat, egg, and soy during preg-nancy did not differ in familieswith andwithout parental atopy (seeTable E7 in this article’s OnlineRepository atwww.jacionline.org).

Sensitization, allergy, and asthmaThe 616 participants with sIgE levels measured at

mid-childhood had similar characteristics to the 1277 studysample (Table I). The most prevalent food allergen sensitizationamong them was to milk (15.9%) followed by peanut (13.8%)(Table I). The most prevalent food allergy was to peanut(4.9%). Twenty-seven (4.6%) specifically reported a peanutallergic reaction (ie, convincing IgE-mediated symptomsfollowing peanut intake, specified as cutaneous, respiratory,cardiovascular, gastrointestinal, and/or anaphylactic symptoms).

Fig 3, A, shows the distribution of food allergen sIgE levelsamong study participants. The range for peanut sIgE levels waswide, spanning less than 0.35 to 423 kU/L.

Sensitization tomultiple food allergenswasmore prevalent thanmonosensitization. Fig 4 summarizes the prevalences of combina-tion food allergen sensitizations. Seventy-seven children (13% ofthe subjects with sIgE levels) were sensitized to 1 food allergenonly, 26 (4.4%) were sensitized to 2 food allergens, 32 (5.4%) to3 food allergens, 16 (2.7%) to 4 food allergens, and 12 (2.0%) toall 5 food allergens. Twenty-nine (19%) of the 155 children sensi-tized to at least 1 food allergen also had food allergy (Fig 3, B).

Association between food allergy, asthma, and

atopic conditionsIn mid-childhood, peanut, wheat, and soy allergy were each

cross-sectionally associated with increased odds of current atopic

Page 4: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

FIG 1. Associations between maternal intake of food allergens during the first trimester and current allergy

and asthma outcomes at mid-childhood. Models were adjusted for child age, sex, breast-feeding history,

parental atopy, and maternal education. *Food allergy defined as sensitization to the respective food AND

EpiPen prescribed, except for peanut allergy, which was more specifically defined by convincing symptoms

of a peanut allergic reaction (history of peanut allergy AND a cutaneous, respiratory, cardiovascular,

gastrointestinal, and/or anaphylactic symptom following peanut ingestion). �Food sensitization defined as

an sIgE level of 0.35 kU/L or more to the respective food.

J ALLERGY CLIN IMMUNOL

MAY 2014

1376 BUNYAVANICH ET AL

dermatitis (ORs, 5.8 to 8.1), current asthma (ORs, 6.4 to 7.0), andcurrent allergic rhinitis (ORs, 3.6 to 4.4) (Fig 5; see Table E8in this article’s Online Repository at www.jacionline.org).Milk allergy was associated with increased odds of asthma(OR, 5.4; 95% CI, 1.3-23.1).

DISCUSSIONIn this prospective prebirth cohort study of participants unse-

lected for atopic propensity, higher maternal intakes of allergenicfoods during early pregnancy were associated with lower risks ofallergy and asthma in mid-childhood. Maternal peanut intakeduring the first trimester was associated with a 47% reduction inthe odds of childhood peanut allergic reaction; maternal milkintake during the first trimester was associated with reduced oddsof childhood asthma and allergic rhinitis; and maternal intake ofwheat during the second trimester was associated with reduced

childhood atopic dermatitis. We did not detect associationsbetween maternal egg or soy intakes and childhood outcomes.We also observed that allergies to these 5 foods in childhood wereassociated with concurrent asthma and atopic disease.

Our results support the hypothesis that maternal diet duringearly pregnancy affects allergy and asthma outcomes inmid-childhood. Our study is distinct from previous work forseveral reasons. Most previous studies on this topic wereconducted in European populations,10-12,15-18,39-41 which havedifferent trends in atopy42 and different lifestyles.43 US-basedstudies addressing this issue selected subjects from atopicfamilies13,31 or relied on distant recall of diet during pregnancyafter the child’s food allergy status was known.13 Overall, moststudies examining the effect of maternal diet on child atopyselected subjects from atopic families10-14 or recruited subjectswith the aim of examining asthma and allergy.15,17,18,44 The topichas been examined in general birth cohort studies, but with

Page 5: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

FIG 2. Associations between maternal intake of food allergens during the second trimester and current

allergy and asthma outcomes at mid-childhood. Models were adjusted for child age, sex, breast-feeding

history, parental atopy, and maternal education. *Food allergy defined as sensitization to the respective

food AND EpiPen prescribed, except for peanut allergy, which was more specifically defined by

convincing symptoms of a peanut allergic reaction (history of peanut allergy AND a cutaneous,

respiratory, cardiovascular, gastrointestinal, and/or anaphylactic symptom following peanut ingestion).

�Food sensitization defined as an sIgE level of 0.35 kU/L or more to the respective food.

J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 5

BUNYAVANICH ET AL 1377

limitations; a UK-based general birth cohort study relied ondistant recall of pregnancy diet after study enrollment,39 and aDanish general birth cohort study did not assess maternal dietbefore the 25th week of pregnancy.40 In that study, Maslovaet al40 found that midpregnancy nut intake was associated withdecreased odds of asthma and allergic rhinitis, although theydid not examine other foods or outcomes other than asthma andallergic rhinitis. We found no other studies that examinedmaternal diet before 25 weeks, with most assessing diet for thelast month or last trimester of pregnancy only,10-16,18 and mostrelying on distant recall of diet after the child’s birth and afterstudy enrollment.13,16,39 Thus, a strength of our study is the pro-spective collection of dietary information at 2 time points duringpregnancy. In addition, to assess the potential longer term effectsof such exposures, we examined outcomes in mid-childhood.Most of the previous studies examined outcomes in the initial

year(s) of life only, assessing for allergy and asthma ininfancy,12,13 at 18 months,10 2 years,17 3 years,18 and 5 years.11,16

The first trimester is a formative period of fetal immune systemdevelopment.3 Cells with dendritic/macrophage structure arepresent at 4 to 6 weeks.45 Positive and negative selection inT-cell development occur during this time, such that by 15 weeks,human thymocytes express a complete set of T-cell receptors,19

and variable domains of T-cell receptor beta chains areexpressed.46 B cells with surface IgM (sIgM)1 isotypes aredetectable by 9 weeks, and sIgA, sIgG, and sIgD isotypes appearby 10 weeks.20 IgE is made by 11 weeks.47 Thus, early forms ofmany cells involved in allergy are formed during the firsttrimester. Early encounter with food allergens via maternal dietduring this critical period of immune system formation couldlead to tolerance rather than sensitization. Maternal dietaryantigens are known to cross the placenta.48 Maternal diet may

Page 6: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

FIG 3. Food allergen sensitization and food allergy among participants of the Project Viva birth cohort.

A,Distribution of food allergen sIgE levels among the 616 participants for whom sIgE levels weremeasured.

B, Percent of study population sensitized with and without allergy. The total height of each bar represents

the prevalence of sensitization to each food allergen among the 616 participants for whom sIgE levels were

measured. Each bar is then divided into 2 parts—the red part representing the proportion sensitized to the

food allergen and food allergic, and the blue part representing the proportion sensitized to the food allergen

and not food allergic.

J ALLERGY CLIN IMMUNOL

MAY 2014

1378 BUNYAVANICH ET AL

influence TH-cell differentiation as well as fetal airway differen-tiation.4 For example, some studies report associations betweenmaternal intake of antioxidants and wheezing, asthma, allergensensitization, lung function, and exhaled nitric oxide.26,49,50 Ourobservation of a 47% reduced odds of peanut allergic reaction

with each z score of peanut intake in the maternal first-trimesterdiet, and a 15% reduced odds of asthma and allergic rhinitiswith each z score of milk intake in the maternal first-trimesterdiet, are consistent with these developmental principles. Sucheffects may be food-specific due to distinct nutrients in each

Page 7: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

FIG 4. Prevalences of single and multiple food allergen sensitization. Numbers are percent of study sample

with mid-childhood data and sIgE levels (N 5 616).

FIG 5. Cross-sectional associations between food allergy and current asthma, current allergic rhinitis, and

current atopic dermatitis at mid-childhood. Models were adjusted for child age, sex, breast-feeding history,

parental atopy, and maternal education. Association for egg allergy and atopic dermatitis not shown given

0 subjects with both conditions at mid-childhood.

J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 5

BUNYAVANICH ET AL 1379

food. For example, peanut contains high levels of linoleic acid, anessential fatty acid that has been associated with T-cell signaling,MHCII expression, and production of arachidonic acid andprostaglandins.51 Milk is the main food source for vitamin D,andmaternal vitamin D intake has been associated with decreasedchildhood wheezing in this cohort.25 Although many previousstudies found no association between maternal diet duringpregnancy and childhood outcomes,6,8-12,18,39 their null results

could be because maternal diet before 25 weeks of pregnancywas not assessed. Consistent with this hypothesis, we observedstrongest associations with our first-trimester data.

In contrast to our findings, some studies observed a positiveassociation between high peanut intake during pregnancy andchild atopic outcomes.13-16,44 For example, a Dutch birth cohortstudy of asthma and dust mite allergy reported increased asthmain children whose mothers had daily versus rare intake of nut

Page 8: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

J ALLERGY CLIN IMMUNOL

MAY 2014

1380 BUNYAVANICH ET AL

products during the last month of pregnancy.15 Sicherer et al13

observed that maternal recall of frequent third-trimester peanutingestion was associated with peanut sensitization in childrenwith existing egg or milk allergy. Frank et al44 reported increasedpeanut allergy, atopic dermatitis, and other food sensitization inchildren from atopic families whose mothers recalled frequentpeanut intake during pregnancy. Our findings may differ fromthese earlier findings because (1) we targetedmaternal diet duringearly rather than late pregnancy; (2) we administered FFQs duringpregnancy, reducing recall bias; and/or (3) our participants wereunselected for atopic propensity.

The 5.6% prevalence of mid-childhood food allergy in ourstudy population is consistent with data from the National HealthInterview Survey showing increasing rates of food allergy in theUnited States, from 3.4% in 1997-1999 to 5.1% in 2009-2011.1

The 2005-2006 National Health and Nutrition ExaminationSurvey (NHANES) estimated food allergy prevalence to be3.8% among 6- to 19-year-olds.22 Gupta et al52 reported a higherrate of overall food allergy (8.0%). These differences likely reflectmethodology,53 as the National Health Interview Survey definedfood allergy using parental report,1 NHANES relied on sIgElevel,22 and Gupta et al52 used subject-reported history. Becausefood allergy is not accurately reported by patients, the expertpanel sponsored by the National Institute of Allergy andInfectious Disease recommends that objective measurements beused to establish a true diagnosis of food allergy.7 We requiredboth elevated food sIgE level and prescribed EpiPen to define afood allergy, and we had specific questions targeting convincingsymptoms of peanut allergic reaction.

We recognize that rates of specific food allergies that we reportare higher (eg, peanut 4.9%) than those previously reported.22,52

We believe our results are valid for several reasons. First, the prev-alence of peanut allergic reaction (ie, convincing IgE-mediatedsymptoms after peanut ingestion) was 4.6% in our study, whichis similar to our peanut allergy prevalence. Assessment of foodallergy based on report of convincing IgE-mediated reactionsymptoms such as those covered by our questions has beenpreviously shown to have a low false-positive rate.29 Therefore,our similar rates of peanut allergy and peanut allergic reactionsupport our strategy of using elevated sIgE levels andprescribed EpiPen for defining a specific food allergy. Second,the odds of food allergy are higher in the Northeast54 and inurban areas55; our subjects came from mostly urban easternMassachusetts. Third, the estimated prevalence of clinical allergyto peanut, milk, and egg was lower among 6- to 19-year-olds inNHANES (eg, peanut allergy 2.7%). While the 6- to 19-year-old category overlaps with the mean age of our cohort (7.9 years),it includes many older individuals, and the prevalence of foodallergy is generally lower in older age groups.22 Fourth, selectionbias may have caused children with allergies and other pediatricdiseases to present for the mid-childhood visit, as comparedwith healthy children. Finally, food allergy is increasinglyprevalent, and our results could be consistent with this trend.1

Apart from NHANES,21,22 limited data are available on foodsensitization in the general US population.22 Sensitization tomultiple food allergens (14.5%) was more prevalent thanmonosensitization (13%) in our cohort. This was not observedin NHANES,22 but NHANES did not examine sensitization tosoy and wheat, common childhood food allergens that we studiedin addition to peanut, milk, and egg. Our study reports rates ofcombination cosensitizations to the common childhood food

allergens in a US population unselected for atopy or any disease,which we have not seen reported. Consistent with previousobservations, many sensitized subjects were also not clinicallyallergic to the relevant food allergen.21,22

Food allergy, asthma, allergic rhinitis, and atopic dermatitiscommonly occur in combination, which we observed andquantified. Previous studies have demonstrated concurrence ofasthma and food allergy overall, suggesting a relationship due toshared mechanisms, or perhaps a causal link.21 We sought tocharacterize the association between specific food allergies andcurrent atopic outcomes, choosing to do so in the same cohortto minimize variation between studies. We observed that peanut,wheat, and soy allergy were all consistently associated withhigher odds of prevalent asthma, allergic rhinitis, and atopicdermatitis. The associations were not uniformly consistent formilk and egg allergies, perhaps due to their lower prevalenceamong our participants. Our results reinforce that clinicianstreating school-age children with peanut, wheat, and soy allergyin particular should screen for comorbid asthma and allergy.

We recognize limitations to our study. Although imperfect, ourdefinition of food allergy based on both sIgE levels and EpiPenprescription status should reflect food allergy better than eitherparameter alone because sensitization alone overestimatesclinical food allergy,21,22 while epinephrine is underprescribedamong those with convincing symptoms of IgE-mediated foodallergy.29 Although 95% predictive sIgE values for clinical foodallergy have been described,56 these were derived from highlyatopic patients referred to allergists for food allergy concerns.Because our study sample had markedly different baselinecharacteristics, the application of such predictive values to definefood allergy in our cohort was deemed unwise because it wouldlikely lead to misclassification. Our implemented definitionrequiring diagnostic evaluation and EpiPen prescription afterhealth care provider evaluation may in fact represent more rigorthan real-world practice, where 30% of reported food allergy isnot diagnosed by a physician and 23% is not evaluated bydiagnostic testing.57 We recognize the limitation that subjectssensitized to more than 1 food allergen and prescribedEpiPen may have been classified as having more than 1 foodallergy when they may have had only 1. Although we couldcorroborate our definition for peanut allergy with our specificquestions targeting convincing IgE-mediated symptoms thatwould characterize a peanut allergic reaction, we did not haveanalogous questions targeting reaction symptoms to milk, wheat,egg, and soy. Our results for nonpeanut allergies shouldtherefore be interpreted with caution. We plan to ask questionstargeting reaction symptoms to foods other than peanut goingforward as we follow this prebirth cohort into adolescence.Another limitation is the number of children with IgEmeasurements. Although there were no differences in thecharacteristics of these children with the bigger sample, wecannot fully rule out selection bias in the analysis. In addition,we did not administer FFQs during the third trimester,although theoretically and empirically, early pregnancy is likelyto be a more sensitive period for the development of atopicpredisposition. Our study examined multiple outcomes, andwe performed multiple tests, and so our findings should becautiously interpreted in this light. Finally, our results are froman observational longitudinal prebirth cohort study; further studyusing a randomized, controlled interventional design will be moreconclusive.

Page 9: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 5

BUNYAVANICH ET AL 1381

Although many clinicians and researchers believed thatmaternal dietary restrictions during pregnancy and lactation anddelayed introduction of allergenic foods to infants couldprevent atopic disease,5 systematic reviews do not supportthese interventions.6,8 Recent guidelines acknowledge thatthere are insufficient data to support such restrictions.6-9,58 Infact, evidence is accumulating that early introduction ofpeanut, egg, wheat, milk, and fish to the infant diet—rather thandelay or avoidance—may be helpful in inducing tolerance ratherthan allergy.58-63 Our findings suggest potential benefits toincluding peanut, milk, and wheat in the maternal diet duringpregnancy.

Key messages

d The relationship between maternal diet and childhoodallergy and asthma is controversial.

d In a US prebirth cohort unselected for any disease, highermaternal intake of peanut, milk, and wheat duringearly pregnancy was associated with reduced odds ofmid-childhood allergy and asthma.

d Our findings do not support avoidance of specific foodsduring pregnancy to prevent allergy and asthma inchildren. Inclusion of these foods could be beneficial forallergy and asthma prevention.

REFERENCES

1. Jackson KD, Howie LD, Akinbami LJ. Trends in allergic conditions among

children: United States, 1997–2011. Bethesda, Md: National Center for Health

Statistics Data Brief, Centers for Disease Control and Prevention; 2013; 1-7,

Available at: http://www.cdc.gov/nchs/data/databriefs/db121.pdf. Accessed May

6, 2013.

2. Akinbami L, Moorman JE, Baily C, Zahran HS, King M, Johnson CA, et al.

Trends in asthma prevalence, health care use, and mortality in the United States,

2001–2010. Bethesda, Md: National Center for Health Statistics Data Brief,

Centers for Disease Control and Prevention; 2012; 1-8, Available at: http:

//www.cdc.gov/nchs/data/databriefs/db94.htm. Accessed August 30, 2013.

3. Maheshwari A, Calhoun DA. The development of immune cells in the fetus and

neonate. Available at: http://www.uptodate.com/contents/the-development-of-

immune-cells-in-the-fetus-and-neonate. Accessed May 7, 2013.

4. Devereux G. The increase in the prevalence of asthma and allergy: food for

thought. Nat Rev Immunol 2006;6:869-74.

5. American Academy of Pediatrics, Committee on Nutrition. Hypoallergenic infant

formulas. Pediatrics 2000;106:346-9.

6. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during pregnancy or

lactation, or both, for preventing or treating atopic disease in the child. Cochrane

Database Syst Rev 2012;CD000133.

7. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al.

Guidelines for the diagnosis and management of food allergy in the United

States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol

2010;126:S1-58.

8. Thompson RL, Miles LM, Lunn J, Devereux G, Dearman RJ, Strid J, et al. Peanut

sensitisation and allergy: influence of early life exposure to peanuts. Br J Nutr

2010;103:1278-86.

9. Greer FR, Sicherer SH, Burks AW. American Academy of Pediatrics Committee

on Nutrition, American Academy of Pediatrics Section on Allergy and

Immunology. Effects of early nutritional interventions on the development of

atopic disease in infants and children: the role of maternal dietary restriction,

breastfeeding, timing of introduction of complementary foods, and hydrolyzed

formulas. Pediatrics 2008;121:183-91.

10. Falth-Magnusson K, Kjellman NI. Development of atopic disease in babies whose

mothers were receiving exclusion diet during pregnancy–a randomized study.

J Allergy Clin Immunol 1987;80:868-75.

11. Falth-Magnusson K, Kjellman NI. Allergy prevention by maternal elimination

diet during late pregnancy–a 5-year follow-up of a randomized study. J Allergy

Clin Immunol 1992;89:709-13.

12. Herrmann ME, Dannemann A, Gruters A, Radisch B, Dudenhausen JW,

Bergmann R, et al. Prospective study of the atopy preventive effect of

maternal avoidance of milk and eggs during pregnancy and lactation. Eur

J Pediatr 1996;155:770-4.

13. Sicherer SH, Wood RA, Stablein D, Lindblad R, Burks AW, Liu AH, et al.

Maternal consumption of peanut during pregnancy is associated with peanut

sensitization in atopic infants. J Allergy Clin Immunol 2010;126:1191-7.

14. Zeiger RS, Heller S, Mellon MH, Forsythe AB, O’Connor RD, Hamburger RN,

et al. Effect of combined maternal and infant food-allergen avoidance on

development of atopy in early infancy: a randomized study. J Allergy Clin

Immunol 1989;84:72-89.

15. Willers SM, Wijga AH, Brunekreef B, Kerkhof M, Gerritsen J, Hoekstra MO,

et al. Maternal food consumption during pregnancy and the longitudinal

development of childhood asthma. Am J Respir Crit Care Med 2008;178:124-31.

16. Erkkola M, Nwaru BI, Kaila M, Kronberg-Kippila C, Ilonen J, Simell O, et al.

Risk of asthma and allergic outcomes in the offspring in relation to maternal

food consumption during pregnancy: a Finnish birth cohort study. Pediatr Allergy

Immunol 2012;23:186-94.

17. Sausenthaler S, Koletzko S, Schaaf B, Lehmann I, Borte M, Herbarth O, et al.

Maternal diet during pregnancy in relation to eczema and allergic sensitization

in the offspring at 2 y of age. Am J Clin Nutr 2007;85:530-7.

18. Venter C, Pereira B, Voigt K, Grundy J, Clayton CB, Higgins B, et al. Factors

associated with maternal dietary intake, feeding and weaning practices, and the

development of food hypersensitivity in the infant. Pediatr Allergy Immunol

2009;20:320-7.

19. George JF Jr, Schroeder HW Jr. Developmental regulation of D beta reading

frame and junctional diversity in T cell receptor-beta transcripts from human

thymus. J Immunol 1992;148:1230-9.

20. Dorshkind K, Montecino-Rodriguez E. Fetal B-cell lymphopoiesis and the

emergence of B-1-cell potential. Nat Rev Immunol 2007;7:213-9.

21. Branum AM, Lukacs SL. Food allergy among children in the United States.

Pediatrics 2009;124:1549-55.

22. Liu AH, Jaramillo R, Sicherer SH, Wood RA, Bock SA, Burks AW, et al. National

prevalence and risk factors for food allergy and relationship to asthma: results

from the National Health and Nutrition Examination Survey 2005-2006.

J Allergy Clin Immunol 2010;126:798-806.e13.

23. Oken E, Kleinman KP, Berland WE, Simon SR, Rich-Edwards JW, Gillman MW.

Decline in fish consumption among pregnant women after a national mercury

advisory. Obstet Gynecol 2003;102:346-51.

24. Fawzi WW, Rifas-Shiman SL, Rich-Edwards JW, Willett WC, Gillman MW.

Calibration of a semi-quantitative food frequency questionnaire in early

pregnancy. Ann Epidemiol 2004;14:754-62.

25. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST,

Gold DR, et al. Maternal intake of vitamin D during pregnancy and risk of

recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007;85:788-95.

26. Litonjua AA, Rifas-Shiman SL, Ly NP, Tantisira KG, Rich-Edwards JW,

Camargo CA Jr, et al. Maternal antioxidant intake in pregnancy and

wheezing illnesses in children at 2 y of age. Am J Clin Nutr 2006;84:

903-11.

27. Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al.

International Study of Asthma and Allergies in Childhood (ISAAC): rationale

and methods. Eur Respir J 1995;8:483-91.

28. Warner JO. Peanut allergy: a major public health issue. Pediatr Allergy Immunol

1999;10:14-20.

29. Sicherer SH, Munoz-Furlong A, Burks AW, Sampson HA. Prevalence of peanut

and tree nut allergy in the US determined by a random digit dial telephone survey.

J Allergy Clin Immunol 1999;103:559-62.

30. Nwaru BI, Hickstein L, Panesar SS, Muraro A, Werfel T, Cardona V, et al. The

epidemiology of food allergy in Europe: a systematic review and meta-analysis.

Allergy 2014;69:62-75.

31. Zeiger RS, Heller S. The development and prediction of atopy in high-risk

children: follow-up at age seven years in a prospective randomized study of

combined maternal and infant food allergen avoidance. J Allergy Clin Immunol

1995;95:1179-90.

32. Milner JD, Stein DM, McCarter R, Moon RY. Early infant multivitamin

supplementation is associated with increased risk for food allergy and asthma.

Pediatrics 2004;114:27-32.

33. United States Census Bureau. Current Population Survey (CPS). 2013. Available

at: http://www.census.gov/hhes/www/cpstables/032012/hhinc/hinc01_000.htm.

Accessed May 1, 2013.

34. Centers for Disease Control and Prevention. Lifetime asthma prevalence percents

by age, United States. 2011 National Health Interview Survey (NHIS) Data. 2011.

Available at: http://www.cdc.gov/asthma/nhis/2011/table2-1.htm. Accessed

November 12, 2013.

Page 10: Peanut, milk, and wheat intake during pregnancy is ...allergo.lyon.inserm.fr/ALLERGOLOGIE_Pediatrique/1.8.3.consommation_lait.pdf · Food, drug, insect sting allergy, and anaphylaxis

J ALLERGY CLIN IMMUNOL

MAY 2014

1382 BUNYAVANICH ET AL

35. Wallace DV, Dykewicz MS, Bernstein DI, Blessing-Moore J, Cox L, Khan DA,

et al. The diagnosis and management of rhinitis: an updated practice parameter.

J Allergy Clin Immunol 2008;122:S1-84.

36. Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the

United States: data from the 2003 National Survey of Children’s Health.

J Invest Dermatol 2011;131:67-73.

37. Bunyavanich S, Soto-Quiros ME, Avila L, Laskey D, Senter JM, Celedon JC.

Risk factors for allergic rhinitis in Costa Rican children with asthma. Allergy

2010;65:256-63.

38. Belsley D, Kuh E, Welsch RE. Regression diagnostics: identifying influential data

and sources of collinearity. New York: Wiley; 2004.

39. Lack G, Fox D, Northstone K, Golding J. Avon Longitudinal Study of Parents and

Children Study Team. Factors associated with the development of peanut allergy

in childhood. N Engl J Med 2003;348:977-85.

40. Maslova E, Granstrom C, Hansen S, Petersen SB, Strom M, Willett WC, et al.

Peanut and tree nut consumption during pregnancy and allergic disease

in children—should mothers decrease their intake? Longitudinal evidence

from the Danish National Birth Cohort. J Allergy Clin Immunol 2012;130:

724-32.

41. Nwaru BI, Ahonen S, Kaila M, Erkkola M, Haapala AM, Kronberg-Kippila C,

et al. Maternal diet during pregnancy and allergic sensitization in the offspring

by 5 yrs of age: a prospective cohort study. Pediatr Allergy Immunol 2010;21:

29-37.

42. Venter C, Hasan Arshad S, Grundy J, Pereira B, Bernie Clayton C, Voigt K, et al.

Time trends in the prevalence of peanut allergy: three cohorts of children from the

same geographical location in the UK. Allergy 2010;65:103-8.

43. Hadley C. Food allergies on the rise? Determining the prevalence of food

allergies, and how quickly it is increasing, is the first step in tackling the problem.

EMBO Rep 2006;7:1080-3.

44. Frank L, Marian A, Visser M, Weinberg E, Potter PC. Exposure to peanuts in

utero and in infancy and the development of sensitization to peanut allergens

in young children. Pediatr Allergy Immunol 1999;10:27-32.

45. Foster CA, Holbrook KA, Farr AG. Ontogeny of Langerhans cells in human

embryonic and fetal skin: expression of HLA-DR and OKT-6 determinants.

J Invest Dermatol 1986;86:240-3.

46. Bonati A, Zanelli P, Ferrari S, Plebani A, Starcich B, Savi M, et al. T-cell receptor

beta-chain gene rearrangement and expression during human thymic ontogenesis.

Blood 1992;79:1472-83.

47. Punnonen J, Aversa GG, Vandekerckhove B, Roncarolo MG, de Vries JE.

Induction of isotype switching and Ig production by CD51 and CD101 human

fetal B cells. J Immunol 1992;148:3398-404.

48. Loibichler C, Pichler J, Gerstmayr M, Bohle B, Kisst H, Urbanek R, et al.

Materno-fetal passage of nutritive and inhalant allergens across placentas of

term and pre-term deliveries perfused in vitro. Clin Exp Allergy 2002;32:

1546-51.

49. Martindale S, McNeill G, Devereux G, Campbell D, Russell G, Seaton A.

Antioxidant intake in pregnancy in relation to wheeze and eczema in the first

two years of life. Am J Respir Crit Care Med 2005;171:121-8.

50. Devereux G, Turner SW, Craig LC, McNeill G, Martindale S, Harbour PJ, et al.

Low maternal vitamin E intake during pregnancy is associated with asthma in

5-year-old children. Am J Respir Crit Care Med 2006;174:499-507.

51. Yaqoob P, Calder PC. Fatty acids and immune function: new insights into

mechanisms. Br J Nutr 2007;98:S41-5.

52. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, et al. The

prevalence, severity, and distribution of childhood food allergy in the United

States. Pediatrics 2011;128:e9-17.

53. Sicherer SH. Epidemiology of food allergy. J Allergy Clin Immunol 2011;127:

594-602.

54. Rudders SA, Espinola JA, Camargo CA Jr. North-south differences in US

emergency department visits for acute allergic reactions. Ann Allergy Asthma

Immunol 2010;104:413-6.

55. Gupta RS, Springston EE, Smith B, Warrier MR, Pongracic J, Holl JL.

Geographic variability of childhood food allergy in the United States. Clin Pediatr

(Phila) 2012;51:856-61.

56. Sampson HA. Utility of food-specific IgE concentrations in predicting

symptomatic food allergy. J Allergy Clin Immunol 2001;107:891-6.

57. Gupta RS, Lau CH, Sita EE, Smith B, Greenhawt MJ. Factors associated with

reported food allergy tolerance among US children. Ann Allergy Asthma

Immunol 2013;111:194-8.e4.

58. Fleischer D, Spergel JM, Assa’ad AH, Pongracic JA. Primary prevention of allergic

disease through nutritional interventions. J Allergy Clin Immunol 2013;1:29-36.

59. Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, et al.

Early consumption of peanuts in infancy is associated with a low prevalence of

peanut allergy. J Allergy Clin Immunol 2008;122:984-91.

60. Koplin JJ, Osborne NJ, Wake M, Martin PE, Gurrin LC, Robinson MN, et al. Can

early introduction of egg prevent egg allergy in infants? A population-based

study. J Allergy Clin Immunol 2010;126:807-13.

61. Poole JA, Barriga K, Leung DY, Hoffman M, Eisenbarth GS, Rewers M, et al.

Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics

2006;117:2175-82.

62. Katz Y, Rajuan N, Goldberg MR, Eisenberg E, Heyman E, Cohen A, et al.

Early exposure to cow’s milk protein is protective against IgE-mediated cow’s

milk protein allergy. J Allergy Clin Immunol 2010;126:77-82.e1.

63. Alm B, Aberg N, Erdes L, Mollborg P, Pettersson R, Norvenius SG, et al. Early

introduction of fish decreases the risk of eczema in infants. Arch Dis Child 2009;

94:11-5.